Oades, R. D., (2006).
Neurobiology and neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD): mechanisms and pharmacological treatment.
Journal of Psychopharmacology, 20, A4 (S14).

Introduction: An appreciation of the neurobiology underlying the ways in which a disorder differs from the normal should be a preliminary to understanding and improving on existing and helpful medication. Approaches to attention-deficit/hyperactivity disorder (ADHD) include the techniques of neurophysiology, of imaging the anatomical and functional correlates of the status and function of brain regions and the effects of pharmacological challenge.
a) Electrophysiology and fMRI. In resting ADHD subjects, there is usually a more or a less broad increase of EEG slow activity in relation to fast oscillations. Studies of the coherence between these signals in different parts of the brain suggest that a sub-group is showing a delay in maturation of the underlying neural structures. Numerous studies of the potentials associated with processing stimuli point to an unusual asymmetry of development, with delays or impairment often located on the right side. These differences, evident in change-detection, delay- and stop-tasks are often observed in fMRI studies and highlight potential contributions from inferior frontal and cingulate function to the difficulties of ADHD subjects.
b) Neuroimaging and the monoamines. The presumed action of methylphenidate on the dopamine transporter and well-publicised but controversial genetic evidence for biased transmission of a transporter polymorphism seem to be supported by PET studies reporting reduced binding potentials in the midbrain and right ventral striatum. However, in addition, there is not only evidence for altered mesocortical dopamine transmission via the D4 binding site, but that noradrenergic neurons (that are equally affected by methylphenidate and take up extrasynaptic dopamine) contribute to anomalous cortical function. It is difficult to overlook that alpha-2 agonism reduces distractibility, hyperactivity and enhances associative learning, behavioural inhibition, and impulse control. But there is also good experimental and some genetic evidence for a relevant role of serotonin activity in controlling cognitive impulsivity.
c) Intra-individual variability and neuron-glia energy supply. Could the characteristics and symptoms of ADHD - rated as presenting often, frequently, pretty much, most of the time – reflect a rather different type of disturbance? The variability of expression and performance over brief time periods (milliseconds to seconds) may be a core problem. Russell and colleagues (Russell VA, Oades RD, Tannock R. et al. (2006) Behavioural and Brain Functions, in press) propose an explanation. They suggest that there is a deficiency of the energy supply to rapidly firing cortical neurons. Central to the mechanism may be the lactate shuttle under astrocytic control and modulated by monoaminergic input. If confirmed the relevant mechanisms offer a whole range of new targets for genetic moderation and therapeutic intervention.